Technical Field
The present invention relates to a bone graft comprising a tannin-hydroxyapatite resin scaffold, osteocompetent stem cells, and a growth medium, and methods of use.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present invention.
Tannin and its derivatives can be used in various applications [U.S. Pat. No. 9,302,413; WO2014117946 A1; Lacoste, C., et al., Pine tannin-based rigid foams: Mechanical and thermal properties, Industrial Crops and Products, 2013, 43, 245; WO2013010668 A1; US20150361240; US20150274921; US20150259460; U.S. Pat. No. 6,043,350; US20140193322; US20140158927; US20060194918; Szczurek, A., et al., The use of tannin to prepare carbon gels. Parts I: Carbon aerogels, Carbon, 2011, 49, 2773; Szczurek, A., et al., The use of tannin to prepare carbon gels. Parts II: Carbon aerogels, Carbon, 2011, 49, 2785; Amaral-Labat, G., et al., Pore structure and electrochemical performances of tannin-based carbon cryogels, Biomass Bioenergy, 2012, 39, 274; Grishechko, L. I., et al., New tannin-lignin aerogels, Industrial Crops and Products, 2013, 41, 347—each incorporated herein by reference in its entirety], because their mechanical properties can vary in a wide range, depending on their method of preparation. Among others materials, tannin and tannin compounds have been approved for human use and have been accepted as totally non-toxic and environmentally friendly by the European commission REACH program and European Food Safety Authority (EFSA) [Ajinomoto OmniChem, Impact of REACh on Ajinomoto OmniChem's Natural Specialties, http://www.natural-specialities.com/PDF/Applications/REACh%20compliance%20OmniChem%20Natural%20Specialties%20v3.0.pdf, 2009; European Food Safety Authority, Scientific Opinion on the safety and efficacy of tannic acid when used as feed flavouring for all animal species, EFSA Journal, 2014, 12, 3828—each incorporated herein by reference in its entirety]. Tannins can be very soft materials such as the organic resin used as a “formaldehyde-free cornstarch-tannin adhesive” [Moubarik, A., et al., Preparation and Mechanical Characterization of Particleboard made from Maritime Pine and Glued with Bio-Adhesives based on Cornstarch and Tannins, Maderas Ciencia y Technologia, 2010, 12, 189; Basso, M. C., et al., A New Approach to Environmentally Friendly Protein Plastics and Foams, Bioresources, 2015, 10, 8014—each incorporated herein by reference in its entirety], or very hard materials such as grinding discs [Lagel, M. C., et al., Cutting and grinding wheels for angle grinders with a bio-resin matrix solid grinding wheels, Industrial Crops and Products, 2015, 67, 264—incorporated herein by reference in its entirety] and automobile brake pads [Lagel, M. C., et al., Automotive brake pads made with a bio resin matrix, Industrial Crops and Products, 2015, 85, 372—incorporated herein by reference in its entirety].
The need for bone tissue substitutes for dental, craniofacial, and orthopedic reconstructions is rapidly increasing due to rapid global population growth and extension of life expectancy, with the number of elderly people (+65 years) estimated to be about 2 billion by 2050 [Clegg, A. et al., Frailty in elderly people, The Lancet, 2013, 381, 752—incorporated herein by reference in its entirety]. Available options to treat bone deficiencies are based on transplantation of bone grafts or implantation of alloplastic materials [Hing, K. A., Bone repair in the twenty-first century: biology, chemistry or engineering?, Philos Trans A Math Phys Eng Sci., 2004, 362, 2821—incorporated herein by reference in its entirety], which can restore tissue integrity and functionality but fail to provide optimal therapeutic solutions in several clinical cases, such as in situations characterized by extensive tissue loss, poor bone quality, or otherwise compromised regenerative capacity [Oreffo, R. O., et al., Future potentials for using osteogenic stem cells and biomaterials in orthopedics, Bone, 1999, 25, 5S—incorporated herein by reference in its entirety]. Conversely, engineering bone substitutes by culturing osteocompetent cells onto compliant biomaterials offers the possibility to grow unlimited amounts of tissue products with enhanced regenerative potential and broader clinical use [de Peppo G. M., et al., Engineering bone tissue substitutes from human induced pluripotent stem cells, Proc Natl Acad Sci USA. 2013, 110, 8680—incorporated herein by reference in its entirety].
Interfacing osteocompotent stem cells onto porous tannin spray-dried powder (PTSDP) resin scaffolds holds the potential to enhance the healing properties of these materials. However, currently available PTSDP scaffolds lack macroporosity, a critical feature that allows cell infiltration, communication, and growth. Scaffold porosity can also facilitate bone ingrowth and remodeling, therefore maximizing the therapeutic potential of tissue-engineered products. Specifically in bone engineering, porosity is important for developing biomaterial scaffolds that mimic the architecture of the native bone tissue.
In view of the forgoing, one objective of the present disclosure is to provide a bone graft comprising a tannin-hydroxyapatite resin scaffold, osteocompetent stem cells, and a growth medium, and methods of use.